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Exp Brain Res (2005) 165: 328342

DOI 10.1007/s00221-005-2309-7


F. Hellstrom S. Roatta J. Thunberg M. Passatore

M. Djupsjobacka

Responses of muscle spindles in feline dorsal neck muscles

to electrical stimulation of the cervical sympathetic nerve

Received: 12 January 2005 / Accepted: 8 February 2005 / Published online: 10 May 2005
 Springer-Verlag 2005

Abstract Previous studies performed in jaw muscles of responses were not secondary to changes in extrafusal or
rabbits and rats have demonstrated that sympathetic fusimotor activity. Further data showed that the sym-
outow may aect the activity of muscle spindle aer- pathetically induced modulation of MSA discharge was
ents (MSAs). The resulting impairment of MSA infor- not secondary to the concomitant reduction of muscle
mation has been suggested to be involved in the genesis blood ow induced by the stimulation. Hence, changes
and spread of chronic muscle pain. The present study in sympathetic outow can modulate the aerent signals
was designed to investigate sympathetic inuences on from muscle spindles through an action exerted directly
muscle spindles in feline trapezius and splenius muscles on the spindles, independent of changes in blood ow. It
(TrSp), as these muscles are commonly aected by is suggested that such an action may be one of the
chronic pain in humans. Experiments were carried out in mechanisms mediating the onset of chronic muscle pain
cats anesthetized with alpha-chloralose. The eect of in these muscles in humans.
electrical stimulation (10 Hz for 90 s or 3 Hz for 5 min)
of the peripheral stump of the cervical sympathetic nerve Keywords Sympathetic nervous system
(CSN) was investigated on the discharge of TrSp MSAs Muscle spindle Myalgia Neck muscles
(units classied as Ia-like and II-like) and on their re- Motor control
sponses to sinusoidal stretching of these muscles. In
some of the experiments, the local microcirculation of
the muscles was monitored by laser Doppler owmetry.
In total, 46 MSAs were recorded. Stimulation of the Introduction
CSN at 10 Hz powerfully depressed the mean discharge
rate of the majority of the tested MSAs (73%) and also Data reported on experimental animal models have
aected the sensitivity of MSAs to sinusoidal changes of shown that proprioceptive information from some
muscle length, which were evaluated in terms of ampli- muscle territories can be impaired by activation of the
tude and phase of the sinusoidal tting of unitary sympathetic nervous system (SNS). In particular, acti-
activity. The amplitude was signicantly reduced in Ia- vation of eerent sympathetic pathways was shown to
like units and variably aected in II-like units, while in aect aerent activity of muscle spindle aerents
general the phase was aected little and not changed (MSAs) in jaw-elevator muscles of rabbits (Passatore
signicantly in either group. The discharge of a smaller et al. 1996; Roatta et al. 2002) and rats (Matsuo et al.
percentage of tested units was also modulated by 3-Hz 1995). The interpretation of the few data reported on
CSN stimulation. Blockade of the neuromuscular junc- hindlimb muscles is controversial in that the sympathetic
tions by pancuronium did not induce any changes in action was considered either relevant and directly
MSA responses to CSN stimulation, showing that these exerted on spindles (Francini et al. 1978; Hunt 1960),
small and therefore of scarce signicance in motor
F. Hellstrom and S. Roatta equally contributed to this work. function (Hunt et al. 1982), or secondary to the vaso-
constriction and consequent muscle hypoxia produced
F. Hellstrom J. Thunberg M. Djupsjobacka by the stimulation (Eldred et al. 1960; Hunt et al. 1982).
Centre for Musculoskeletal Research, Gavle University,
Umea, Sweden Although generally characterized by depression of
stretch sensitivity, the responses of MSAs to sympathetic
S. Roatta (&) M. Passatore stimulation showed some variability in the dierent
Department of Neuroscience-Physiology Division,
University of Torino Medical School, Torino, Italy studies in terms of latency, time course, and magnitude
E-mail: of the eects. Therefore, the need exists to study the

eect of sympathetic action on other territories and spontaneously uctuate, when muscle tonus increased in
species while also checking whether such eects could be the right hindlimb, and/or when a withdrawal reex was
related to the concomitant vascular action. initiated as a response to nociceptive pinching of the
It is well known that proprioceptive information hindlimb paw. Tracheotomy was performed, and end-
from muscle spindles is important for control and expiratory CO2 was continuously monitored. The sys-
coordination of ongoing movements and posture (Abe- temic ABP, monitored via a catheter inserted into the
lew et al. 2000; Bove et al. 2002; Cordo et al. 1994; Ghez left femoral artery, was maintained above 80 mmHg,
and Sainburg 1995) as well as for programming move- and when necessary by infusion of dextran (Macrodex,
ments (Bard et al. 1995; LaRue et al. 1995). In masti- 6% with sodium chloride, Pharmacia), glucose (55 mg/
catory muscles, the proprioceptive impairment produced ml) with sodium chloride, or sodium chloride acetate
by stimulation of sympathetic pathways was shown to into the left femoral vein. The left hindlimb was com-
induce a consistent reduction of the myotatic reex pletely denervated to avoid aerent input from ischae-
(Grassi et al. 1993a, 1993b) and also to aect more mic necrotic tissues. The body temperature was
complex motor patterns, such as the masticatory maintained between 37C and 38C through heating
movements evoked by stimulation of the cortical mas- lamps and a hot water cushion positioned under the
ticatory area in rabbits (Roatta et al. 2004). It is there- animals belly.
fore reasonable to hypothesize that a strong sympathetic The dorsal neck muscles on the left side were exposed
activation and the ensuing depression of spindle aerent by a midline longitudinal incision of the skin, which was
activity may aect motor control and reduce eciency in carefully denervated around the neck, and of the prox-
muscle use. imal part of the ipsilateral forelimb. The maximum
On this basis, the sympathetic modulation of motor physiological length of the ipsilateral trapezius and
function has been recently taken into account among the splenius (TrSp) muscles was measured in situ, then both
factors responsible for chronic myalgia (Roatta et al. muscles were freed from the surrounding tissues,
2002; Passatore and Roatta 2003; Johansson et al. 2003), disconnected from their insertions to the skull, and
a complex and multifactorial syndrome whose patho- attached to an electromagnetic puller through a wire
physiology and etiology are scarcely known. This (Fig. 1). The longissimus capitis, biventer cervicis, and
hypothesis is motivated by the following: (1) Epidemi- occipitoscapularis muscles were removed bilaterally. The
ological studies report the frequent association between suboccipital muscles and the intervertebral muscles were
the development of chronic myalgias and stressful removed bilaterally to expose the dorsal aspect of the
working environments (reviewed by Punnett and Gold cervical vertebral column. To gain access to the dorsal
2003), and (2) functional studies report, in human sub- roots, a laminectomy was performed between C2 and
jects aected by chronic myalgia in the neck-shoulder C6. All exposed tissues were covered with paran oil,
area, disturbances in the control and coordination of which was held at a temperature of about 38C. The
ongoing movements that are attributed to deterioration skull and the cervical part of the vertebral column were
of proprioceptive information (Madeleine et al. 2004; immobilized by clamps connected to a rigid metal frame.
Michaelson et al. 2003). Among the possible causes of In some experiments, the neuromuscular blocking
the deterioration of proprioceptive information, sym- agent pancuronium bromide (1 mg/kg, administered
pathetic hyperactivity due to stress and pain should intravenously and repeated when needed) was given, and
therefore be taken into account. the cat was articially ventilated to maintain the end-
The aim of the present study was to investigate, in the tidal CO2 concentration at preparalysis levels.
cat, whether stimulation of the sympathetic supply to Alpha-adrenergic blockade was performed in three
neck muscles aects the activity and sensitivity of MSAs experiments by intravenous injection of phentolamine
of splenius and trapezius muscles. methanesulfonate (Sigma, 2.53.5 mg/kg). In two cats,
the left subclavian artery, ipsilateral to the recorded MSA
units, was isolated, and a plastic snare was placed around
Methods it so that it could be temporarily occluded to produce
hypoxia in the TrSp muscles. The location of the occlusion
All procedures were performed in accordance with was veried during the autopsy. At the end of the exper-
Swedish law and were approved by the Ethical Com- iments, all cats were sacriced by intravenous adminis-
mittee on Animal Experiments at the University of tration of a lethal dose of pentobarbital sodium.
Umea (Sweden). The experiments were performed on 17
adult cats anesthetized with alpha-chloralose (initial
dose 60 mg/kg). To keep a sucient depth of anesthesia, Preparation and stimulation of the cervical
heart rate and arterial blood pressure (ABP) were sympathetic nerve
continuously monitored, and withdrawal reexes were
estimated every 15 min. Additional doses of alpha- The cervical sympathetic nerve (CSN) ipsilateral to the
chloralose (25 mg/kg) were administered whenever isolated TrSp muscles was dissected free from
indications of a reduced level of anesthesia were pres- surrounding tissues, and the depressor nerve, cut low in
entwhen heart rate and ABP increased or began to the neck, and its peripheral stump were placed in a

Fig. 1 a Schematic picture of the registration set-up. Muscle Recording and analysis
spindle aerents (MSAs) originating from the trapezius and
splenius muscle, isolated from dorsal roots, are placed on silver-
wire recording electrodes. The muscles are connected to an Functionally single muscle aerents from the ipsilateral
electromagnetic puller. The head is xed to a metal frame. b TrSp muscles were isolated from cut laments of the
Schematic drawings of how muscle spindle aerent discharge was dorsal roots C3 and C4, and their activity was recorded
quantied during sinusoidal stretches (1 Hz; peak ampli- using silver-wire electrodes, amplied, and collected on
tude=1 mm). The stretch-evoked MSA activity was quantied by
tting a sine function to a spike density histogram, in which spikes computers using an input-output interface device (CED
from four consecutive cycles were collected (the algorithm is 1401 power) with 16-bit AD-converter. The data
described in the appendix). The following were derived from the acquisition was performed by use of the program Spike
quantication: mean discharge rate (MDR, number of spikes 2 (CED). The activity of two to four units was recorded
divided by time duration of the interval considered, in pulses per
second [PPS]), peak amplitude (AMP, in PPS), and phase of the at the same time.
tting sine function (PHASE, in deg). PHASE is equal to the phase All units were routinely tested with a sequence of
lead of the tting sine function with respect to the sinusoidal muscle dierent stimuli in order to provide a basis for their
length signal classication. After prestretching the muscle to 8 mm
(maximum physiological length=0 mm), the muscle was
cylindrical polyethylene cu containing two platinum- further stretched with ramp-and-hold (R&H) stimuli
stimulating electrodes mounted 2 mm apart. The cu, (amplitude=4 mm, rise time=2 s, plateau dura-
lled with warm mineral oil and covered with cotton tion=6 s, passive tension developed <300 g). In addi-
soaked in mineral oil for further insulation, was xed to tion, after prestretching the muscle to 2 mm, slow sine
the surrounding tissue. Then the muscles and skin of the waves (1 Hz, 1-mm peak amplitude) and 100-Hz and
neck were carefully stitched over the electrode cylinder 150-Hz vibrations (amplitude 90140 lm and 3050 lm,
assembly. The CSN was routinely stimulated at 10 Hz respectively) were applied. Aerent units were classied
for 90 s and occasionally at 3 Hz for 5 min with 7 V as (1) Ia-like if they responded 1:1 to the 100-Hz
(0.4-ms pulse width). Successive stimulation trials were vibration and exhibited silencing of discharge during the
separated by at least 15 min to allow for recovery. The shortening phase of the slow sine wave and during the
eectiveness of CSN stimulation was assessed through- release phase of the R&H, or (2) II-like if they did not
out the experiment by checking pupillary responses and respond 1:1 to 100-Hz vibration and continued ring
monitoring blood ow changes in muscle-cutaneous during the release phase of sine waves and R&H. In
tissues of the cheek through an inductive proximity addition, the location of each receptor was assessed by
sensor (Selet Sensor Mod. 18/5 OC, Turin, Italy) recording the units response to gentle pressure by a
working as a surface plethysmograph (Roatta et al. probe on dierent areas of the muscle. Conduction
1996). The CSN isolation was performed before turning velocity measurements were not performed because of
the cat into the prone position and progressing with the short conduction distance and the lack of bimodality
dorsal root preparation. in the ber diameter spectrum (Price and Dutia 1989;

Richmond and Abrahams 1979). All units classied as stimulation, during the recovery period, depending on
nonmuscle spindles were discarded. In particular, units the time, when the MDR started to return toward
exhibiting high discharge thresholds to stretch stimulus control value (late phase).
and failing to maintain a tonic ring during the hold Possible changes in extrafusal muscle ber activity of
phase of the R&H were excluded, as this pattern is more the TrSp muscles were indirectly assessed by monitoring
typical of Golgi tendon organs (GTOs) (Jami 1992; the force output from the muscles through a force
Richmond and Abrahams 1979). However, the non- transducer connected to the electromagnetic puller
parallel orientation of the muscle bers in TrSp muscles (sensitivity=0.01 N). In seven cats, trials were per-
causes the applied stretches to be detected dierently by formed to investigate whether the actions induced by
receptors positioned in dierent muscle areas. For the sympathetic stimulation on the MSA discharge could be
same reason, the classical GTO identication technique secondary to the hypoxic condition induced by the
based on the response to muscle twitch, attempted in a concomitant vasoconstriction. In these experiments,
few experiments, proved to be ineective, also due to the microvascular blood ow was measured by a laser
incomplete muscle contraction elicited by direct muscle Doppler owmeter (PeriFlux PF 2b, Perimed, Sweden)
stimulation (Richmond and Abrahams 1979). Therefore, via a needle probe (PF 302) that estimates microcircu-
we cannot exclude that some GTOs may have been lation within a tissue hemisphere having a radius of
erroneously identied as muscle spindles. However, the 11.5 mm. The probe was inserted into the trapezius or
low ratio of GTO/MSAs reported for cat neck muscles, splenius muscle, close to the location (see above) of at
8/129 (Richmond and Abrahams 1979), makes the least one of the muscle spindles currently recorded. In
inclusion of GTOs in the muscle spindle sample rather this group of trials, a particular muscle spindle aerent
unlikely. was discarded whenever this maneuver drastically
While testing the eect of CSN stimulation, the changed either its discharge frequency or its pattern of
TrSp muscles were subjected to sinusoidal stretches discharge, which was interpreted as a sign that the probe
(1 Hz; peak-to-peak amplitude=2 mm), which were had produced a lesion. During the trial in which the
superimposed on the plateau of large R&H stretches probe was inserted, the muscle was kept in a xed po-
(from 10 mm to the plateau at 2 mm; plateau sition; that is, sinusoidal stretches were not delivered in
duration=60 s). The R&H stretches were separated by order to avoid movement artifacts and damages in
short intervals of 13 s. The stretch-evoked MSA microcirculation by the probe. In two of these experi-
activity was quantied by means of a least square ments, the subclavian artery was occluded to induce a
tting, with a 1-Hz sine function, of the spike density large sudden reduction or abolition of blood supply to
histogram generated from a single MSA. This analysis the TrSp muscles.
was performed over intervals including four consecu- Statistical analysis was performed using two non-
tive cycles, each interval being moved one cycle for- parametric tests, the Wilcoxon signed rank test and the
ward with respect to the previous interval. In this way, Mann-Whitney U-test (signicance level at 0.05 in all
a time resolution of 1 s was achieved in the estimate tests). The Wilcoxon signed rank test was used to
of the tting parameters. The tting algorithm adop- investigate the eect of CSN stimulation on MDR,
ted is a modied version of the classical spike-density AMP, and PHASE in the early and late periods com-
cycle histogram tting (Matthews and Stein 1969; pared with control within either Ia-like or II-like units,
Hulliger et al. 1977) and is described in the appendix. as well as to investigate the eects of neuromuscular
The following parameters were then extracted from junction blockade on the changes induced by CSN
the t: (1) the mean rate of discharge (MDR, number stimulation. The Mann-Whitney U-test was used for
of spikes divided by time duration of the interval investigating dierences in MDR, AMP, and Phase
considered, in pulses per second [PPS]); (2) the during control, early, and late periods in relation to unit
amplitude of the tted sine function (AMP, peak type (Ia-like or II-like). All statistics were conducted
amplitude of the tted sine function, in PPS; (3) the using the SPSS statistical package.
phase advance of the tted sine function with respect
to the input (muscle length) signal (PHASE, in
degrees), a zero value corresponding to perfect align- Results
ment between the two traces (Fig. 1).
The eects of CSN stimulation on MSA discharge According to our identication procedure, 46 spindle
were evaluated by assessing the changes exhibited by units were classied as Ia-like (n=33) or II-like
the above parameters during and after CSN stimula- (n=13). In the control condition (before CSN stimu-
tion. The parameters were time-averaged over 2040-s lation), Ia-like units diered from II-like units in
intervals positioned in the following sequence: (1) 40 s having a signicantly lower MDR (26.511.5 PPS vs.
before the start of CSN stimulation (control); (2) 37.77.0 PPS, P<0.01), a higher stretch sensitivity
around the point of maximum eect on the MDR (AMP: 22.67.5 PPS vs. 10.25.3 PPS, P<0.01),
(early phase); (3) 100300 s after the end of CSN and a slightly higher dynamic sensitivity as evidenced

by the larger phase lead (PHASE: 64.413.4 vs. Another example of rapid depression is shown in
51.110.3, P<0.01). Fig. 3 (upper panel). The least common pattern of
response to CSN stimulation, occurring in only three
units, consisted of a slight increase in MDR coupled
Eects of CSN stimulation at 10 Hz with either a decrease (two units) or an increase (one
unit) in amplitude modulation (AMP) in response to
Stimulation of the CSN was tested on the discharge of sinusoidal muscle stretch (see below).
all 46 MSAs (33 Ia-like and 13 II-like) innervating To quantify possible changes in stretch sensitivity,
spindles located in TrSp muscles. Two to four dierent sinusoidal stretches were continuously delivered to the
units were often recorded at the same time so that their muscle in 38 (27 Ia-like and 11 II-like) of the 46 tested
response to the same CSN stimulation trial could be units, and the unit responses to CSN stimulation were
compared. CSN stimulation at 10 Hz lasting 90 s evaluated whenever possible in terms of AMP and
changed the MDR in 34 of the 46 MSAs tested (73%). PHASE of the sine-tted discharge rate (see Methods).
The remaining 12 units were unresponsive to the stim-
ulation. Both responsive and unresponsive units were
recorded during the same experiments, in some cases Early eect
simultaneously. An example of the most common re-
sponse pattern is shown in Fig. 2a (thick line), with the As mentioned above, the most common pattern of
stimulation period indicated by the solid black line be- response, occurring in 30 of the 46 tested units, consisted
neath the time axis. In general, the eect consisted of a of a powerful depression in MDR that usually outlasted
strong depression of the discharge rate, hereafter termed the stimulation time. In 21 units, the depression was
early eect, followed by a fast partial recovery, which strong enough to completely silence the unit for a period
often began with a transient excitatory rebound of ranging from 5 s to 160 s, during which the aerent
varying size. Thereafter, the discharge exhibited a long- discharge was not even transiently activated by the
lasting aftereect (late eect) in which it remained ongoing sinusoidal stretch. The latency of the eect was
slightly depressed before returning to the control value, rather long and variable (range 2580 s, mean 50.7 s).
within a time between 30 s and 4 min after the end of This variability could not be attributed to dierent
stimulation. animal conditions because widely dierent latencies also
occurred between dierent units recorded simulta-
neously. In the remaining 16 tested units, the average
decrease in MDR was 21.4% (7.012.4 PPS,
P<0.05), with no signicant dierence between Ia-like
and II-like units. Figure 4a shows the distribution of
these eects for Ia-like (lled circles) and II-like (lled

Fig. 2 Response of a Ia-like muscle spindle aerent (MSA) to

cervical sympathetic nerve (CSN) stimulation while trapezius and
splenius muscles were subjected to sinusoidal stretches. a CSN Fig. 3 Response of a Ia-like muscle spindle aerent (MSA) to
stimulation at 10 Hz for 90 s produces a powerful depression in the stimulation of the cervical sympathetic nerve (CSN) during
mean discharge rate (MDR), the unit falling silent and slowly sinusoidal stretches of trapezius and splenius muscles. The eect
recovering in the late period, after a rebound eect. Similar long- during the early period consists of a complete suppression of the
lasting depression is exhibited by the amplitude of modulation discharge (MDR trace); the response to sinusoidal stretches (AMP
(AMP). b CSN stimulation at 3 Hz for 300 s elicits in the same unit trace) is absent. Notice, however, the dierent time course of the
a similar depressant eect; however, in this case the latency is recovery of these two signals; MDR shows a long-lasting late eect
increased, the duration of the silencing is decreased, and the return whereas AMP quickly returns to control. PHASE cannot be
to the control condition is faster and occurs before the end of the evaluated during the early period, and increases during the long-
stimulation. Sinusoidal stretches: 1 Hz, peak-to-peak ampli- lasting depression of the MDR that follows CSN stimulation.
tude=2 mm. CSN stimulations (7 V) are signaled by horizontal Parameters of CSN stimulation and sinusoidal stretches are as in
bars and vertical dashed lines Fig. 2

squares) units. A high number of units silenced by the eects of CSN stimulation on AMP and PHASE are
CSN stimulation are visible; this eect occurred preva- illustrated in Fig. 4b, c, respectively (lled symbols).
lently in Ia-like units and is independent of initial values In some units, the depressant eect was preceded by a
of MDR. small and transient increase in MDR (see, for instance,
In the many units that rapidly fell silent in response to Fig. 3, upper panel).
CSN stimulation (n=16, out of 38 tested with sine
stimulus), changes in AMP and PHASE could not be
measured. In the remaining 22 units (13 Ia-like, 9 II- Late eect
like), a signicant AMP reduction (19.8%, P<0.05)
occurred only in Ia-like units, which, however, showed The early depressant eect described above terminated
no signicant change in PHASE (+1.44.7). II-like with a fairly rapid return of the MDR toward control
units exhibited both small increases and decreases in values. However, in many cases (31/46), a slight
AMP without signicant average changes (+1.33.7 depression of ring rate persisted for several minutes.
PPS), while exhibiting a small decrease in PHASE Analysis of this late phase (which could now be per-
(3.74.3, P<0.05). Scatter plots describing the formed over all the 38 units tested with the sinusoidal

Fig. 4 Mean discharge rate

(MDR; a), amplitude (AMP; b),
and phase (PHASE; c) of the
tted sine function after cervical
sympathetic nerve (CSN)
stimulation compared with
control (ctrl). Early eect (lled
symbols, on left) and late eect
(open symbols, on right) for all
units divided into Ia-like
(circles) and II-like (squares)
plotted against their own
controls. Diagonal lines
represent no change between
control and early or late eects.
a Ia-like early (n=33), II-like
early (n= 13), Ia-like late
(n=33), II-like late (n=13).
b Ia-like early (n=13), II-like
early (n=9), Ia-like late
(n=26), II-like late (n=11).
c Ia-like early (n=12), II-like
early (n=9), Ia-like late
(n=27), II-like late (n=11)

stimulus) showed that, on average, MDR remained Eects of CSN stimulation at 3 Hz (5 min)
signicantly decreased in the Ia-like group (4.37.1
PPS, 14%, P<0.01) and was not aected in the II- CSN stimulation at 3 Hz was tested on 12 of the units,
like group (2.2% compared with control). The gen- which were modulated by 10-Hz stimulation. Six of
eral picture is shown in Fig. 4a, right, for Ia-like (open them displayed signicant alterations in stretch re-
circle) and II-like (open squares) aerents. On average, sponse, even though the eects were generally smaller
neither Ia-like nor II-like units exhibited signicant and exhibited latencies from stimulus onset, which were
changes in AMP and PHASE. In single trials, a few longer than the ones observed for the routinely applied
net increases or decreases occurred in AMP (equally 10-Hz stimulations. The 3-Hz stimulation did not gen-
represented), while four units showed a clear phase erally succeed in producing a moderate and stable
advance (for example, Fig. 3, bottom panel) ranging inhibition of the ring pattern, rather, in some cases
between 6 and 17 (see Fig. 4b, c, right, open sym- (n=3), it still silenced the receptor (Fig. 2b). The other
bols). six units were unaected by the stimulation. MSAs not
responsive to 10-Hz CSN stimulation did not respond to
the 3-Hz stimulation either.
Correlation among parameters

Scatter plots are shown in Fig. 5 in which sympa- Absence of changes in fusimotor activity
thetically-induced changes in AMP (Fig. 5a) and in and extrafusal activity
PHASE (Fig. 5b) are related to relative changes in
MDR for early (lled symbols, left) and late (open Although electromyographic activity was not recorded
symbols, right) eects in Ia-like (circles) and II-like from the studied muscles, activation of extrafusal bers
(squares) units. In the early eect, some correlation in both anesthetized and anesthetized-curarized prepa-
appears to exist in Ia-like units between the early ef- rations can be excluded because no change in muscle
fect on MDR and the variation of both AMP force was detected during the trials.
(r=0.86, P<0.01) and PHASE (r= 0.89, P<0.01), In addition, to ensure that the observed eects were
although estimated from only nine units (those that not due to changes in extrafusal and fusimotor activity,
were not silenced by CSN stimulation). In the late some of the animals were administered a neuromuscular
eect, only the correlation between PHASE and MDR blocking agent (pancuronium) either throughout the
remains signicant (r=0.77, P<0.01). Conversely, experiment or during part of it. The majority of trials
II-like units never exhibit signicant correlations were performed under neuromuscular blockade (n=31),
between these parameters. and the others in nonblocked preparations (n=15). The

Fig. 5 Relative changes in

amplitude of modulation
(AMP, panel a) and phase
(PHASE, panel b) are plotted
versus the relative change in
mean discharge rate (MDR).
Early eect (lled symbols) is
displayed on the left side, and
late eect (open symbols) on the
right. In all cases, changes are
evaluated with respect to the
control condition. Circles refer
to Ia-like and squares to II-like

data obtained from the two groups did not show sig-
nicant dierences in terms of time course and size of
response to sympathetic stimulation. In addition, in ve
of these units (one II-like and four II-like), the response
to CSN stimulation was tested both before and after
blockade. The blockade could produce a slight decrease
in MDR in the control phase but did not aect the ex-
tent and time course of the response. Therefore, all units
were pooled into one single group for analysis.

Action of alpha-adrenergic blockade

on the sympathetically induced response Fig. 6 Eect of cervical sympathetic nerve (CSN) stimulation on
the discharge of two muscle spindle aerents in trapezius muscle
The eect of CSN stimulation was tested before and and on the microvascular blood ow recorded from an area of the
after alpha-adrenergic blockade by phentolamine on ve muscle close to the location of both the recorded spindles. Unit 1 is
Ia-like, and unit 2 is II-like. Note that the small increase in arterial
MSAs collected from three curarized animals. After the blood pressure (ABP) at the start of stimulation, as well as all
blockade, the muscle-cutaneous vasomotor response to rhythmical changes along the trial, are parallel to the changes in
CSN stimulation was almost completely abolished in all muscle microcirculation, which indicates the high sensitivity of the
animals. Alpha-adrenergic blockade completely abol- intramuscular laser Doppler measurement. CSN stimulation at
10 Hz (7 V, 90 s) is signaled with a horizontal bar and vertical
ished the response to sympathetic stimulation in all dashed lines. Microvascular blood ow is calibrated in arbitrary
MSAs tested. units (a.u.)

Tests for vasomotor eects early eect of CSN stimulation should be much shorter.
This was never the case. In addition, the recovery of the
Tests were performed to assess whether sympathetically discharge of both units took place while the blood ow
induced vasoconstriction, and the potentially resulting in trapezius was still close to zero, due to the maintained
hypoxic condition, could be responsible for the observed arterial occlusion. The only dierence between the two
eects on MSA discharge. conditions is that the eect of CSN stimulation lasted
During eight CSN stimulation trials, performed in longer in the trial performed during occlusion, which is
ve experiments, microvascular blood ow was mea- explained by the fact that the washout of the released
sured from the muscle area containing the MSAs being catecholamines was slower than in the control condition.
recorded. In some of these trials, two dierent MSAs The above data indicate that the sympathetically induced
located close to each other (approximate distance 1 cm) modulation of MSA discharge was not secondary to
were simultaneously recorded while the blood ow was the concomitant reduction of muscle blood ow.
measured. One of these trials is shown in Fig. 6. Sym-
pathetic stimulation induced a powerful depression of
the discharge of the unit labeled unit 1 and did not Discussion
substantially aect unit 2, while producing a large de-
crease in blood ow. After the end of stimulation, the The present study has shown, for the rst time, that the
discharge of unit 1 steeply increased again, while the SNS can strongly aect the proprioceptive aerent
blood ow remained reduced. information from MSAs in cat neck muscles. The pat-
In two experiments, the following trials were per- terns of response to stimulation of the sympathetic
formed while recording from MSAs located in trapezius nerves were fairly homogeneous and mainly consisted of
muscle. One of these trials is shown in Fig. 7. Standard a marked depression of MSA discharge, which was more
CSN stimulation was performed (Fig. 7a) and then re- prominent in Ia-like than in II-like units and often
peated under condition of muscle hypoxia (Fig. 7b), that strong enough to completely suppress the activity of the
is, 3 min after starting the occlusion of the ipsilateral MSAs. Whenever such depression silenced the MSA, the
subclavian artery, which was maintained for 78 min stretch sensitivity could not be assessed. Such an
altogether. This occlusion practically eliminated the ow assessment was thus restricted to a small number of units
in the area of trapezius muscle, where both tested spin- that were not silenced during the early phase and ex-
dles were located. The comparison between these two tended to all units during the recovery period (late ef-
trials shows that the latency and the onset of the fect). These assessments revealed a signicant decrease
depressant response (early eect) to CSN stimulation in the amplitude of the sine-tted discharge rate in Ia-
were identical for both MSAs. If the muscle hypoxia per like units in the early eect, while the phase was on
se were responsible for the eect induced by CSN average aected but little.
stimulation, occlusion (Fig. 7b) should modify the MSA The following aspects of the present ndings are in
discharge during the rst 3 min, and the latency of the agreement with other recent studies (Matsuo et al.

Fig. 7 Comparison of the

responses of the same two Ia-
like MSAs from trapezius
muscle to cervical sympathetic
nerve (CSN) stimulation
performed in control (a) and in
hypoxic conditions induced by
occlusion of the ipsilateral
subclavian artery (b). The laser
Doppler needle probe
measuring microvascular blood
ow was inserted into the
trapezius muscle, in an area
close to both spindles whose
aerent activity was recorded.
Note that the response of the
two units is very similar in the
two conditions in terms of
latency and magnitude of the
eect; the longer duration of the
eect under hypoxic condition
is motivated by the slower
washout in the latter condition
due to the persistent drastic
reduction-zeroing in blood
ow. The displacement of the
cheek surface (surf. pleth.),
routinely used as a surface
plethysmography record
(Roatta et al. 1996; see
Methods) shows that CSN
stimulation was eective in
reducing blood volume in
masseter muscle in both trials;
the small decrease in the
amplitude of this response, as
well as the artifacts visible on
both this and on the ow
record, are due to some
stretching of the common
carotid artery during the
subclavian artery occlusion
maneuver. CSN stimulations
(10 Hz, 7 V, 90 s) are signaled
by horizontal bars and vertical
dashed lines

1995; Roatta et al. 2002). We found that the dis- However, at partial variance with results reported on
charge of 73% of the tested MSAs was modulated by jaw muscles, the present data did not show a consistent
sympathetic stimulation, which is comparable to the sympathetic eect on MSA stretch sensitivity as inves-
values of 85% reported for rabbit jaw muscles (Ro- tigated with continuously supplied sinusoidal muscle
atta et al. 2002) and 68% for rat jaw muscles (Ma- stretch. In the few Ia aerents that did not fall silent
tsuo et al. 1995). All studies describe a prevalently after sympathetic stimulation, the stretch response
depressant eect on MSAs, although with dierent amplitude (AMP) was decreased proportionally to the
latencies and time courses. This depression may be relative change in the MDR, suggesting that both eects
responsible for the decrease in the reex muscle re- could be produced by the same depressant mechanism.
sponse to stretch or vibration that was observed However, the observation that a few II-like units
during sympathetic stimulation and intraarterial cate- exhibited clearcut changes in stretch sensitivity, both in
cholamine injection (Francini et al. 1978; Grassi et al. terms of amplitude and phase, unrelated to changes in
1993a, b; Matsuo et al. 1995). In addition, as in MDR, suggests that these eects may be mediated by
rabbit jaw muscles, the eect of sympathetic stimu- dierent mechanisms. Such eects as well as other
lation was independent of gamma eerent activity and smaller eects, such as the initial increase in MDR often
appeared to be largely mediated by alpha-adrenore- observed, might have been masked in many instances by
ceptors. the main depressant eect.

Potential mechanisms served in the dierent preparations. For instance, the

density as well as the distance between the terminals
An increasing body of evidence shows that the SNS is releasing catecholamines and the eectors could dier
involved not only in the traditionally recognized veg- for the spindles of dierent muscles or animal spe-
etative functions but also in modulating the somatic cies, in analogy with what has been reported in
sensitivity and thus sensorimotor integration. In par- other sympathetically innervated structures. Thus, the
ticular, the SNS has been reported to aect the gen- density and nerve varicosity-smooth muscle cell sep-
eration and transmission of sensory information from aration of cerebral and ear arterial beds in the rabbit
a number of mechanical and chemical receptors are reported by Dodge et al. (1994) to vary by a
through an action exerted at the receptor level (re- factor of up to ve. In these studies, they attribute
viewed by Akoev 1981; Koltzenburg 1997). In some to the lower density of sympathetic terminals and to
cases, the ndings have been supported by morpho- the higher terminal-eector distances found in the
logical data. Ballard (1978) and Barker and Saito middle cerebral artery territory the weaker action
(1981) described adrenergic terminals in the spindle exerted by the sympathetic innervation on cerebral
capsule that were not associated with intracapsular blood vessels, compared with the ear territory. At
blood vessels but were either adjacent to sensory present, no morphological data are available on
endings or in neuroeective association with intrafusal terminal-eector distances in muscle spindles, how-
bers. Similar evidence has recently been obtained on ever.
human muscle spindles, in which the noradrenaline Sympathetic modulation of muscle-spindle activity
cotransmitter NPY has been identied in intrafusal might take place at dierent receptor sites, such as the
bers of lumbrical muscles (L.-E. Thornell, personal gamma neuromuscular junction, the intrafusal muscle
communication). ber, the aerent receptive terminal, or the aerent
The present results on cat neck muscles add to the encoding site. Because the eects were not altered by
few previous studies reporting a modulatory action of blockade of the neuromuscular junction, a modulating
sympathetic stimulation and catecholamine injection action at the gamma endplate can be excluded. In a
on MSAs from cat hindlimb muscles (Eldred et al. recent paper on rabbit jaw muscles (Roatta et al.
1960; Francini et al. 1978; Hunt 1960; Hunt et al. 2002), an action at the level of the aerent ber was
1982) and from jaw muscles in rabbit and rat (Matsuo hypothesized because the sympathetically induced
et al. 1995; Passatore et al. 1996; Roatta et al. 2002). depression of the MSA activity overpowered the
However, there is still no general agreement concern- excitation induced by the succinylcholine-mediated
ing the mechanism of such an action regarding whe- contraction of intrafusal bers. This possibility de-
ther the observed eects are due to a direct action on serves additional considerations. Several studies have
the receptor (Francini et al. 1978; Matsuo et al. 1995; shown that calcium channels, in addition to sodium
Passatore et al. 1996; Roatta et al. 2002) or are sec- channels, are involved in generating the receptor po-
ondary to the concomitant reduction of blood ow to tential in MSA terminals. In particular, calcium
the muscle tissue (Eldred et al. 1960; Hunt et al. channel blockers were shown to exert an inhibitory
1982). To our knowledge, no study has been able to action on the amplitude of the receptor potential and
convincingly show that the eects on MSAs are due on the ring frequency in these receptors (Fischer and
to hypoxia consequent to a reduction in blood supply Schafer 2002; Ito et al. 1990; Kruse and Poppele
to the muscle. This point deserves consideration be- 1991). For instance, Fischer and Schafer (2002)
cause, in the present work, the latency of the eect recently found that in isolated muscle spindles, the
was on average longer (50.7 s) than reported by other calcium antagonist nifedipine (at a concentration of
studies, these latencies ranging from 10 s to 45 s in 25 lM) could strongly depress the activity in Ia and II
rabbit jaw muscles (Roatta et al. 2002) and lying be- aerents for several minutes. Although comparisons
low 1 s in rat jaw muscles (Matsuo et al. 1995). We between recordings from MSAs in isolated and in-vivo
tested the possible eect of hypoxia by performing a preparations must be made with caution, the eects of
series of trials with the subclavian artery clamped. The nifedipine are impressively similar to the eects of
virtually complete interruption of blood ow to the CSN stimulation described here (compare their Fig. 2
test muscles did not aect MSA discharge per se, nor with our Fig. 6a, unit 1). The possibility for nor-
did it reduce the latency of the sympathetically in- adrenaline to inhibit Ca2+ inux is well established
duced eect, nor did it prevent the return of spindle and has been demonstrated specically for sensory
discharge to control while the artery was still occluded neurons in dierent animal species (Cox and Dunlap
and the blood ow was still close to zero. These 1992; Dolphin 1995; Marchetti et al. 1986). Therefore,
observations rule out muscle ischemia as a major it may be hypothesized that a noradrenaline-mediated
cause of the observed sympathetic eects on spindle modulation of calcium channels underlies the eects
discharge while supporting the hypothesis of a direct produced by CSN stimulation on MSA discharge.
sympathetic action on the spindle. However, specic investigations on the adrenergic
Consequently, other mechanisms should be con- receptors involved and their intracellular pathways are
sidered for explaining the dierence in latencies ob- needed to conrm this hypothesis.

Methodological considerations and physiological Along the same lines, Matre and Knardahl (2003) showed
signicance that proprioceptive acuity at the ankle joint was not re-
duced by sympathetic activation induced either by a cold-
A stimulation frequency of 10 Hz is often considered to pressor test (foot in 7 water for 3.5 min) or glucose
be beyond the physiological range of operation of the ingestion. In contrast, Christou et al. (2004) did observe
eerent sympathetic system, at least in humans (Janig an increase in the uctuations of the pinch-grip force
and Habler 2000a; Maceeld et al. 2003). However, (which had to be maintained at 2% of maximal voluntary
studies performed in animal models, in which reductions contraction) when stressing the subject with electrical
in muscle blood ow produced by reex sympathetic painful stimuli to the contralateral hand. Eectiveness of
activation were compared with eects produced by the stressor was evidenced by both the results of cognitive
sympathetic stimulation at dierent frequencies, showed assessment and by the signicant increase in the plasma
that the eects of strong sympathetic activation were concentrations of stress hormones (epinephrine, norepi-
reproduced by electrical stimulations in the range of 8 nephrine, ACTH). This result clearly indicates a decrease
10 Hz, and estimates of maximum physiological fre- in the precision in the control of muscle force in stress
quencies reached 1520 Hz (Folkow 1952; Kendrick conditions. In other studies, stressors of various qualities
et al. 1972; Mellander and Johansson 1968). Moreover, and intensities have been shown to impair motor per-
in the anesthetized cat, a condition known to depress formances in humans, with the same stressor eliciting
sympathetic outow, unitary sympathetic bers of the dierent eects depending on the intensity as well as basal
cervical sympathetic trunk showed spontaneous activity conditions of the subjects anxiety (see, for instance,
at frequencies between 0.4 and 7.5 PPS, with an average Noteboom et al. 2001; Sade et al. 1990).
around 2 PPS (Janig and Schmidt 1970; Mannard and The variability of results is likely related to the dif-
Polosa 1973; see also Janig 1985 for review), while in the ferent tests of sympathetic activation used. As pointed
anesthetized rabbit, the same types of ber responded to out above, dierent stressful stimuli likely produce
hypoxia by increasing their average discharge rate from dierent actions on the sympathetic outow to dierent
2 to 12 PPS (Dorward et al. 1987). These data suggest territories. Moreover, the adequate stimulus for sym-
that the physiological values of sympathetic frequen- pathetic bers supplying muscle spindles is presently
cies are not yet clearly identiable and most likely de- unknown. Therefore, if a given test fails to evoke
pend on the animal species, organ, or body district and changes in MSA discharge and/or proprioception and
on whether pre- or postganglionic activity is considered. motor performance, the possibility should be considered
Of course, the electrical stimulation of a sympathetic that the resulting change in sympathetic outow is
nerve diers from physiological sympathetic activation inadequate in terms of type, intensity, or duration.
in another respect. With electrical stimulation, all sym-
pathetic bers are excited synchronously at a constant
frequency; while physiologically the sympathetic bers Concluding remarks
may be recruited partially and variably, re asynchro-
nously and preferentially in bursts. Moreover, sympa- The data collected in trapezius and splenius muscles, as
thetic bers are now known to be dierentially controlled well as similar data reported previously on jaw and some
in dierent territories, organs, and tissues, depending on hindlimb muscles (see above), suggest a direct depressant
the context and type of stressful stimulus (for review and action exerted by the sympathetic system on MSAs.
references, see Janig and Habler 2000b; Morrison 2001), These data also suggest that such sympathetic action is
and their action is in general potentiated by circulating not conned to certain muscles or animal species but
catecholamines. For all the above reasons, CSN stimu- likely is a general feature of the control of MSA dis-
lation is a poor approximation of physiological sympa- charge under conditions producing an increase of sym-
thetic activation, and the pattern of response observed pathetic outow, such as stress. This action would
may not faithfully predict the MSA behavior occurring potentially impair the dierent body functions in which
under stressful conditions. Nevertheless, having ruled muscle spindles play a relevant role, including proprio-
out circulatory mechanisms and having observed similar ception and motor control. In particular, muscle spindles
eects at 3-Hz stimulation frequency, we believe that are known to mediate moment-to-moment control of
increased sympathetic outow under physiological con- muscle length through the fast spinal negative feedback
ditions may entail a depression of MSA activity. loops that also mediate the stretch reex. Activation of
Several research groups have recently investigated the sympathetic system would, in this respect, reduce the
possible alterations in proprioception or motor control in gain of this control, a condition considered useful for
healthy humans in whom increases in sympathetic achieving stability in rapidly executed movements
activity were provoked by stimuli of dierent types (Prochazka 1989), such as a ght-or-ight reaction. In
(Christou et al. 2004; Maceeld et al. 2003; Matre and dierent motor contexts, however, including ne move-
Knardahl 2003). Inspiratory capacity apnea and maximal ments requiring stability and precision, the reduced
expiratory apnea, maneuvers increasing muscle sympa- control of muscle length may be detrimental. This
thetic nerve activity, did not aect MSA activity as de- condition of worsened motor control may call for
tected by microneurography (Maceeld et al. 2003). alternative and suboptimal motor strategies, such as the

cocontraction of agonists and antagonists muscles, Consider the cycle divided into n bins, the center of
aimed at increasing joint stiness and limb stability the ith bin being located at the angle hi (1 i n) and
(Gribble et al. 2003). In turn, these altered motor strat- the bin width being D h=2p/ n radians. A cycle histo-
egies and postures may in the long run lead to muscu- gram is generated from the spike activity of a single
loskeletal problems and diseases. In fact, cocontraction MSA collected over four consecutive cycles. The jth
as well as low-intensity long-duration static contractions spike occurs at a time tj, which corresponds to a specic
are recognized among the main risk factors for the angle hj =2pf tj within the cycle, 1 j m, with m
development of myalgias (Hagg 1991; Rissen et al. 2000, being the total number of spikes collected from the
see Sjogaard et al. 2000 and Van Dieen et al. 2003 for current sample. The number of spikes collected into the
review). ith bin, Yi, divided by the number of cycles (nc=4) and
Numerous experimental and clinical data suggest a the bin width in seconds (Dt=1/(nf)), yields bin contents
correlation between chronic muscle pain of various ori- in terms of spike densities.
gins and disturbances in motor coordination and pro- The histogram thus obtained is tted with a sine wave
prioception, particularly in the cervical region (e.g., whose amplitude, phase, and oset are to be determined
Eriksson et al. 2004; Karlberg et al. 1995; Michaelson by the tting algorithm. For mathematical convenience,
et al. 2003; Revel et al. 1991, 1994; Thunberg et al. 2001; we dened this sine wave by the sum of three terms: a
Wenngren et al. 1998; for review and references, see sine (in phase with the length stimulus), a cosine (90 in
Djupsiobacka 2003; Blair 2003; Johansson et al. 2003). advance of the length stimulus), and a constant term, C,
The data presented in this study may be interpreted to corresponding to the mean ring rate (bias):
suggest that the sympathetically-induced derangement
of proprioceptive information may be one of the F h A sinh B cosh C 2
mechanisms underlying chronic muscle pain, whichas The three unknown variables (A, B, and C) are deter-
pointed out in the Introductionis frequently associ- mined by solving the system of n equations, dened in
ated with stress conditions. matrix terms as
Acknowledgements We thank Monica Edstrom, Stina Langendoen, Mx Y; 3
and Margareta Marklund for valuable assistance in the experi-
ments; Lars Backstrom and Goran Sandstrom for implementing where M is a numerical matrix, Y is the array of spike
the data processing routines and for technical support; and Pro- densities from the above histogram, and x contains the
fessor Uwe Windhorst for enlightening and fruitful comments on variables to be estimated:
the manuscript. This study was supported by grants from The
Swedish Council for Work Life Research, IngaBritt and Arne 2 3
sinh1 cosh1 1
Lundbergs Forskningsstiftelse, and the Italian Ministry of Scien- 2 3
6 sinh2 cosh2 1 7
tic Research (MIUR). 6 7 A
6 7
M 6 sinh3 cosh3 1 7 x 4 B 5
6 .. .. .. 7
4 . . .5 C 4
 n coshn 1 
nf .
Y array20cY1 Y2 Y3 ..Yn
According to a widely used procedure, the stretch- nc
evoked MSA activity may be quantitatively character-
This system is solved by means of the least-square
ized by constructing a cycle histogram of spike density to
algorithm (LSA), which involves multiplying both sides
which a 1-Hz sine function is tted by means of a least-
with the transpose of M:
square algorithm (e.g., Matthews and Stein, 1969; Hul-
liger et al. 1977). A modied version of this procedure is MT Mx MT Y; 5
described here that grants improved performance in case T
the number of spikes in the histogram is low, such as where M is the transpose of the matrix M, and then
when the discharge rate is low and/or the spike sequence solve for x:
is collected from only a few consecutive cycles. Although
this algorithm does not require the construction of the x MT M1 MT Y 6
histogram, this approach is nevertheless described be- The following matrices are generated in Eq. 5:
cause it helps explain how the algorithm works. 2 P 3
The sinusoidal length stimulus applied to the (neck) n P
n P
sin2 hi sinhi coshi sinhi
muscles was the following: 6 7
6 n 1 1 1 7
6 P Pn P
n 7
Stimulus L sinh; 1 T
M M6 6 sinh cosh cos 2
h cosh i 7

i i i 7
6 1 n 1 1 7
where h is the radian angle: h=x t=2p ft, with x being 4 P Pn 5
sinhi coshi n
the angular velocity, f being the frequency of the sine 1 1
wave (f=1 Hz in our case), and t the time. The range
0<h<2p (radians) corresponds to a single cycle.
n 3 where hj is the angular occurrence of each spike.
Yi sinhi Expressions in Eqs.10 and 11 are then inserted in
6 1 7
6 n 7 Eq. 5, and the nonnite term n is eliminated from both
nf 6 P 7
MT Y 6 Yi coshi 7
7 8 sides. The resulting numerical equation is the one that is
nc 6 1 7 used by the algorithm and solved for x according to
4 Pn 5
Yi Eq. 6. Estimates A, B, and C as dened in Eq. 2 are
1 nally obtained.
Now, by letting the width of the histogram bins ap-
proach zero (Dt 0), i.e., n , the elements in the
MTM matrix (Eq. 7) become denite integrals computed Empty bins
over one cycle (0 h 2p); for instance, for the ele-
ment in row 1, column 1 we get the following: This second part deals with the method applied to ex-
X Z 2p clude empty bins in the silent period, which, if not
1 Xn
n!1 n
excluded, would tend to lower the amplitude of the tted
sin2 hi sin2 hi Dh ! sin2 hi dh;
Dh 1
2p 0 sine (Hulliger et al. 1977).
9 After the sine had been tted, the code checked
whether the amplitude was greater than the baseline
and expression Eq. 7 becomes (=negative swing). The part of the sine with negative
2 R 2 R R 3 values was then excluded in the integral of the sine, and
sin hdh sinhcoshdh sinhdh spikes occurring in the silent period were also ex-
T n 6R R 2
R 7 cluded. So, MTM and MTY were recalculated and solved
M M 4 sinhcoshdh cos hdh coshdh 5
2p R R as before.
sinhdh coshdh 2p
Finally, MDR, AMP, and PHASE (see Methods)
10 were computed from A, B, and C:
Therefore, excluding the common factor n (n ), the
nine elements in the matrix can be exactly solved for h, MDR C;  
resulting in simple constant (numeric) values. p A 12
2 2
As for the MTY vector (Eq. 8), its elements now B
contain an innite number of terms, corresponding to
the innite number of bins, but only m terms will be
dierent from zero, m being the total number of spikes
collected into the histogram. In fact, because the bin Validation
width approaches zero (Dt 0), any bin will contain
either one or zero spike. It is therefore convenient to Comparisons of the classical 24-bin method and the
maintain the discrete form of the MTY matrix and only present algorithm were performed by tting a simulated
sum the nonzero terms: (articially generated) spike train with the following
2P m 3 characteristics: average discharge rate=30 Hz, ampli-
sinhj tude of modulation=10 Hz, frequency of modula-
6 1 7
6 m 7 tion=1 Hz, Phase=0. The better performance of the
nf 6 P 7
M Y 6 coshj 7 11 present algorithm is apparent from Table 1, which
nc 6 1 7;
7 shows the results of the tting in two examples with
4 P m 5
1 dierent sample sizes.

Table 1 Comparisons of the estimates produced by the tting of an articially generated spike train with sinusoidal modulation of the
ring frequency (average discharge rate: 30Hz, amplitude of the sinusoidal modulation: 10 Hz, frequency of the sinusoidal modulation:
1 Hz)

Data sample One cycle (31 spikes) Ten cycles (310 spikes)

Present algorithm Classical 24 bins Present algorithm Classical 24 bins

Mean discharge rate (Hz) 31,000 30,000 31,000 30,900

Amplitude of modulation (Hz) 11,000 12,460 11,000 12,114
Phase (Deg) 0,005 7,943 0,006 2,173

The present algorithm is compared with the classical technique of spikes (2nd and 3rd columns) and 310 spikes (4th and 5th columns).
tting a 24-bin spike density histogram (see text). Two cases are The phase parameter is the phase lead of the tting sine wave with
presented in which data samples of dierent sizes have been used: 31 respect to the modulating sine wave in the simulated data set.

Grassi C, Deriu F, Artusio E, Passatore M (1993a) Modulation of

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